Protection of the brain against regional ischemic insult using barbiturate anesthesia is now established to occur in animals including primates. It is proposed to investigate the possibility that anesthetics might exert similar protective effects on ischemic myocardium. Because anesthetic agents differ widely in their ability to cause reductions in cerebral and myocardial oxidative metabolism, it is necessary to study many different anesthetics in detail. Further, there is increasing evidence that the cerebral protective effect seen with anesthetics may not be due to depression of oxidative metabolism. Because myocardial function and metabolism are more readily amenable to experimental modification, the question can be addressed whether myocardial protection against ischemia (if it occurs at all) is due to specific metabolic depression or to a more general and basic effect. If certain anesthetics are more protective of ischemic myocardium than others, then obvious recommendations can be made for clinical anesthesia in cardiac surgery, and for other surgery in patients with coronary vascular disease. Further, if large doses of anesthetics can be shown to exert significant myocardial protection, therapy for acute myocardial infarction can be considered. The second part of this proposal is to investigate new concepts of hepatic protection from specific halothane hepatotoxicity. Recent information indicates that low hepatic oxygen delivery results in abnormal reductive halothane metabolism and liver injury. We propose to establish hepatic hemodynamic and oxygen delivery limits to provide protection of this organ from this ischemic hepatic anesthetic-induced toxicity. The overall concept being investigated is that anesthetic administration can be predicated upon specific organ protective effects, and that the choice of anesthetic can be determined more cogently depending upon which organ system is most severely compromised.